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BACKGROUND: Oxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs. METHODS: The predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations. RESULTS: There were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007). CONCLUSIONS: An intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA.
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Antioxidantes , Modelos Animais de Doenças , Isoflavonas , Osteoartrite , Estresse Oxidativo , Distribuição Aleatória , Animais , Coelhos , Isoflavonas/farmacologia , Isoflavonas/administração & dosagem , Isoflavonas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteoartrite/prevenção & controle , Injeções Intra-Articulares , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Transtornos da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/prevenção & controle , Articulação Temporomandibular/patologia , Articulação Temporomandibular/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Ácido Iodoacético , Masculino , Tirosina/análogos & derivadosRESUMO
OBJECTIVES: To evaluate the possible impact of RAST on optimal antimicrobial therapy via de-escalation or escalation, and to determine the reduction in antibiotic susceptibility reporting time with RAST. METHODS: In this single-center, prospective descriptive study, RAST was performed on clinical blood cultures containing E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates. Very major error, major error, and categorical agreements with VITEK 2 were analyzed. RESULTS: One hundred and three isolates were included in the study, out of which 29.1â¯% were carbapenem-resistant and 36.9â¯% were multidrug-resistant according to VITEK 2. Categorical agreement of the RAST method with standard antimicrobial susceptibility test (AST) wasâ¯>â¯90â¯% at 6â¯h, except for piperacillin/tazobactam. Antibiotic revision could be carried out in 79.6â¯% of the patients either by de-escalation (61.2â¯%) or escalation (18.4â¯%) for optimal therapy based on the RAST 6â¯h result. RAST could provide carbapenem-sparing therapy in 24â¯% of patients. Reduction in antibiotic susceptibility reporting time was 41.5â¯h (38.8 to 63.2, median (IQR)). CONCLUSIONS: RAST can provide early antibiotic revision in a majority of patients with significantly reduced antibiotic susceptibility reporting time. Six hours is the shortest optimal time for antibiotic revision with RAST. In countries where empirical broad-spectrum antibiotics are prevalent due to high antibiotic resistance pressure, RAST should be proposed primarily in de-escalation and carbapenem-sparing strategies.
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Kisspeptin is an endogenous peptide hormone that is the most potent stimulator of the hypothalamo-pituitary-gonadal (HPG) axis. The HPG axis can be suppressed by the activation of the hypothalamo-pituitary-adrenal (HPA) axis. The physiological role of kisspeptin in the interaction of the HPG axis and the HPA axis is not fully understood yet. The purpose of the current study was to investigate the possible effects of peripheral injection (intraperitoneally) of kisspeptin on HPG axis and HPA axis activity as well. Adult male Wistar rats were randomly divided into seven groups as sham (control), kisspeptin (10 nmol), p234 (10 nmol), kisspeptin + p234, kisspeptin + antalarmin (10 mg/kg), kisspeptin + astressin2b (100 µg/kg), and kisspeptin + atosiban (0.250 mg/kg) (n = 10 each group). At the end of the experiment, the hypothalamus, pituitary gland, and serum samples of the rats were collected. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin and kisspeptin + astressin2b groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin, kisspeptin + antalarmin, kisspeptin + astressin2b, and kisspeptin + atosiban groups that compared to the control group. There was no a significant difference in corticotropic releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone and corticosterone concentrations among all groups. Moreover, no significant difference was found in the concentration of pituitary oxytocin. Our results suggest that peripheral kisspeptin injection induces an activation in the HPG axis, but not in the HPA axis in male rats.
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PURPOSE: In advanced breast cancer, endocrine therapy is preferred in the absence of visceral crisis. Cyclin-dependent kinase inhibitors (CDKi) are the gold standards. The selection of subsequent treatments after CDKi treatment is still controversial, and the efficacy of everolimus (EVE) combinations is unknown. In this study, we aimed to investigate the efficacy of EVE after CDKi administration in real-life experiences. METHOD: The study received data from 208 patients from 26 cancer centers. Demographic and histologic features, diagnosis, progression, last visit dates, and toxicities were recorded. This study was a retrospective case series. RESULTS: One hundred and seven patients received palbociclib, while 101 patients received ribociclib as a CDKi. The overall response and disease control rates of EVE combinations were 60% and 88%, respectively. In univariate analysis, the absence of liver metastasis, age > 40 years, better type of response, and immediate treatment after CDKi were related to increased progression-free survival. Liver metastasis and response type were significantly associated with overall survival. In the multivariate analysis, response remained significant in terms of progression-free survival, while response type, liver metastatic disease, and hematologic toxicity were prognostic in terms of overall survival. CONCLUSION: This study provides evidence of the benefits of EVE combinations after CDKi treatment. EVE combinations may be more appropriate for patients with non-liver metastasis, and the first treatment response shows the benefit of treatment. In addition, immediate treatment after CDKi treatment is more beneficial than later lines of treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Everolimo , Inibidores de Proteínas Quinases , Piridinas , Humanos , Feminino , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Everolimo/uso terapêutico , Pessoa de Meia-Idade , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Purinas/administração & dosagem , Purinas/efeitos adversos , Purinas/uso terapêutico , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Piperazinas/efeitos adversos , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Resultado do Tratamento , Idoso de 80 Anos ou mais , PrognósticoRESUMO
BACKGROUND: This study aimed to compare the acute effects of aerobic exercise performed with blood flow restriction (BFR), a novel method to increase exercise gains, with blood free flow (BFF) conditions in type 2 diabetes mellitus (T2DM). METHODS: Fifteen individuals with T2DM performed BFF and BFR (40% of arterial occlusion pressure) cycling exercises 48 hours apart, at equal intensity (45% heart rate reserve) and duration (38 minutes). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), blood glucose, heart rate, and muscle oxygen saturation (SmO2) were assessed before-after and during exercise sessions. RESULTS: SBP, DBP, and MAP in the overload phase were higher in the BFR group than in the BFF group (Pâ =â .009, 0.031, and 0.013, respectively). Changes in blood pressure (∆SBP and ∆DBP) were similar between the BFF and BFR groups (Pâ >â .05), whereas ∆MAP differed (Pâ =â .016). Changes in blood glucose levels and heart rates were not significantly different between the groups. Although SmO2baseline was lower in the BFR group (Pâ =â .049), SmO2min and SmO2max did not differ significantly between the BFF and BFR groups. CONCLUSION: The similar decrease in blood glucose levels between the groups suggests that BFR exercise is favorable in terms of hypoglycemia. The higher blood pressure observed during the BFR exercise remained within safe limits. These results suggest that people with T2DM can safely perform BFR aerobic exercises; however, further studies are required.
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Glicemia , Pressão Sanguínea , Diabetes Mellitus Tipo 2 , Exercício Físico , Frequência Cardíaca , Humanos , Diabetes Mellitus Tipo 2/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Exercício Físico/fisiologia , Glicemia/análise , Glicemia/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Idoso , Saturação de Oxigênio/fisiologia , Terapia por Exercício/métodos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiopatologiaRESUMO
BACKGROUND: Neoadjuvant treatment is the standard treatment in locally advanced ESCC. However, the optimal chemotherapy regimen is not known. METHOD: This is a retrospective observational cohort study conducted with propensity score matching. Patients with resectable ESCC from 13 tertiary centers from Türkiye were screened between January 2011 and December 2021. We compared the efficacy and safety of neoadjuvant chemoradiotherapy with the CF and the CROSS regimens in patients with ESCC. RESULTS: Three hundred and sixty-two patients were screened. Patients who received induction chemotherapy (n = 72) and CROSS-ineligible (n = 31) were excluded. Two hundred and fifty nine patients received neoadjuvant chemoradiotherapy. After propensity score matching (n = 97 in both groups), the mPFS was 18.4 months (95% CI, 9.3-27.4) and 25.7 months (95% CI, 15.6-35.7; p = 0.974), and the mOS was 35.2 months (95% CI, 18.9-51.5) and 39.6 months (95% CI 20.1-59.2; p = 0.534), in the CF and the CROSS groups, respectively. There was no difference between subgroups regarding PFS and OS. Compared with the CF group, the CROSS group had a higher incidence of neutropenia (34.0% vs. 62.9%, p < 0.001) and anemia (54.6% vs. 75.3%, p = 0.003) in all grades. On the other hand, there was no significant difference in grade 3-4 anemia, grade 3-4 neutropenia, and febrile neutropenia between groups. There were more dose reductions and dose delays in the CROSS group than in the CF group (11.3% vs. 3.1%, p = 0.026 and 34.0% vs. 17.5%, p = 0.009, respectively). The resection rate was 52.6% in the CF-RT and 35.1% in the CROSS groups (p = 0.014). CONCLUSION: Favorable PFS and pCR rates and a comparable OS were obtained with the CROSS regimen over the CF regimen as neoadjuvant chemoradiotherapy in patients with ESCC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fluoruracila , Terapia Neoadjuvante , Paclitaxel , Pontuação de Propensão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante/métodos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Idoso , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Turquia , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , AdultoRESUMO
Background/aim: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Several studies have shown that alterations of microbiota increase the risk of neurodegenerative disorders. We aimed to reveal whether there is a difference in the gut microbiota of patients with ALS. Materials and methods: The participants are divided into three groups. Group 1 comprised patients with ALS. Healthy family members living in the same house of the patients formed Group 2. Lastly, sex- and age-matched healthy people were included in Group 3. Fecal samples were collected in 15-mL falcon tubes and stored at -80 °C. Genomic DNA isolation was performed on samples. Bacterial primers selected from the 16S rRNA region for the bacterial genome and ITS1 and ITS4 (internal transcribed spacer) were used for the identification of DNA. Next generation sequence analysis (NGS) and taxonomic analyses were performed at the level of bacterial phylum, class, order, family, genus, and species. Alpha and beta diversity indexes were used. The linear discriminant analysis (LDA) effect size method (LEfSe) was applied to identify a microbial taxon specific to ALS disease. Results: The relative abundances of the Succinivibrionaceae and Lachnospiraceae families were significantly lower in patients. The dominant families among patients were Streptococcaceae and Ruminococcaceae, while the dominant families among healthy controls were Bacteroidaceae and Succinivibrionaceae. The LEfSe analysis revealed that four families (Atopobiaceae, Actinomycetaceae, Erysipelatoclostridiaceae, Peptococcacceae) differed significantly between the patients and healthy controls (LDA values> 2.5, p < 0.05). Conclusion: Comparison with family members living in the same house is the strength of this study. We found that there were changes in the microbiota of the patients, consistent with the literature. Studies that analyze the composition of the gut microbiota in the predisease period may be needed to understand whether dysbiosis is caused by the mechanisms inherent in the disease or whether it is dysbiosis that initiates the disease.
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Esclerose Lateral Amiotrófica , Microbioma Gastrointestinal , Humanos , Esclerose Lateral Amiotrófica/microbiologia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Fezes/microbiologia , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Idoso , Estudos de Casos e ControlesRESUMO
Because radioactive 177Lu has a wide range of possible applications in radiopharmaceuticals, its removal from medical wastewater is particularly important. Montmorillonite clay was employed as an adsorbent in this study. Radioactive solutions were prepared with dilutions of the solution containing 177Lu at various concentrations, in which it was present as Lu3+. ULEGe detector in gamma spectrometer was used to measure 177Lu gamma rays emitted from the radioactive aqueous solutions. The results obtained showed that it is possible to remove 177Lu with a high yield of approximately 90% and it is effective in a period of 90 min under acidic conditions. From the findings, it can be argued that Montmorillonite clay, as an abundant and sustainable adsorbent, may also be suitable for the disposal of different radioactive medical wastes such as 131I and 99mTc, and also the technique based on gamma ray spectroscopy can be used for fast and practical measurements of radioactive material amounts.
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Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in children. In most previously healthy infants, RSV infection is self-limited and resolves without complications. The risk of bacteremia is low in young febrile infants with RSV infection. Herein, we report two previously healthy infants with severe RSV infection who had concurrent Klebsiella bacteremia.
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We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.
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BACKGROUND: To compare the fat transfer combined with plasma energy and only fat transfer methods for genital rejuvenation and to investigate the efficacy enhancing properties of plasma energy. METHODS: Forty-six patients were equally divided into two groups according to the surgical method as the group A (n = 23) and the group B (n = 23). The patients in the group A received only fat transfer, while the patients in the group B received fat transfer combined with plasma energy. Both groups were scheduled for postoperative follow-up at 1, 3, 6, and 12 months. The lifting effect on the labia majora after the procedure was evaluated with photographs and patient satisfaction questionnaires including the female genital self-image scale (FGSIS). RESULTS: The mean age of all participants was 32.8 ± 5.1 years, and the mean body mass index (BMI) was 24.7 ± 3.4 kg/m2. The mean preoperative FGSIS scores were similar between the groups (p = 0.542). The mean total FGSIS score was 18.8 ± 1.4 in the group A and 18.3 ± 1.5 in the group B in the preoperative period. However, the mean FGSIS scores at 1, 3, and 6 months were significantly higher in the group B than the group A (p = 0.032, p = 0.012, and p = 0.009, respectively). At 6 months of follow-up, the mean total FGSIS score was 20.7 ± 1.4 in the group A and 22.3 ± 1.5 in the group B, indicating a statistically significant difference (p = 0.028). CONCLUSION: This novel technique is a more minimally invasive technique compared to other energy modalities with lower lateral and vertical energy dissipation than other conventional methods, and labia majora fat filling augmentation application can be performed with more permanent and longer-lasting outcomes than fat transfer only. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Tecido Adiposo , Rejuvenescimento , Humanos , Feminino , Adulto , Rejuvenescimento/fisiologia , Tecido Adiposo/transplante , Satisfação do Paciente/estatística & dados numéricos , Resultado do Tratamento , Vulva/cirurgia , Seguimentos , Estética , Técnicas CosméticasRESUMO
Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 µg), kisspeptin + astressin 2B (1 µg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.
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Sistema Hipotálamo-Hipofisário , Kisspeptinas , Sistema Hipófise-Suprarrenal , Ratos Wistar , Animais , Masculino , Kisspeptinas/administração & dosagem , Kisspeptinas/farmacologia , Kisspeptinas/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Fragmentos de Peptídeos/administração & dosagem , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Corticosterona/sangue , Vasotocina/farmacologia , Vasotocina/administração & dosagem , Testosterona/sangue , Injeções Intraventriculares , Gônadas/metabolismo , Gônadas/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Adrenocorticotrópico/sangue , Hormônio Liberador da Corticotropina , OligopeptídeosRESUMO
BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.
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Antimetabólitos Antineoplásicos , Capecitabina , Neoplasias de Mama Triplo Negativas , Humanos , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Quimioterapia Adjuvante/métodos , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Intervalo Livre de Doença , Turquia , Idoso , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasia Residual , Taxa de Sobrevida , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , MastectomiaRESUMO
Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias do Sistema Nervoso Central , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Estudos Retrospectivos , Receptores ErbB/genética , Resultado do Tratamento , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologiaRESUMO
BACKGROUND: Neuroinflammation induced by systemic inflammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-inflammatory properties; however, its effect on systemic inflammation-related neuroinflammation is unknown. OBJECTIVES: This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. METHODS: Six-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1) control, 2) OLE-only, 3) LPS + vehicle, 4) OLE+LPS (O-LPS), and 5) a single-dose OLE + LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fibrillary acidic protein (GFAP) and CD11b immunohistochemistry, nod-like receptor protein-3, interleukin (IL)-1ß, IL-17A, and IL-4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. RESULTS: In both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus (P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group (P < 0.001). Hippocampal GFAP immunoreactivity and IL-17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL-4 concentrations. CONCLUSIONS: OLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL-4 concentrations indicates the induction of an anti-inflammatory phenotype of microglia. OLE may also modulate astrocyte and IL-17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL-17A concentrations when administered with or without LPS.
Assuntos
Interleucina-17 , Glucosídeos Iridoides , Lipopolissacarídeos , Ratos , Animais , Masculino , Lipopolissacarídeos/toxicidade , Ratos Wistar , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Interleucina-17/uso terapêutico , Doenças Neuroinflamatórias , Antioxidantes/metabolismo , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Interleucina-4/uso terapêutico , Hipocampo/metabolismo , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Interleucina-1beta/metabolismo , Microglia/metabolismoRESUMO
BACKGROUND: The effects of housing conditions on animal physiology, behavior or stress are still debated. The aim of this study was to investigate the effects of three different housing systems, individually ventilated cages (IVC), classical small cages with floor surface area of 500 cm2 (CC500) and classical large cages with floor surface area of 800 cm2 (CC800) on body weight, sensory-motor performances, depression-like behavior, plasma corticosterone and brain oxidative stress parameters in C57BL/6 mice. The mice housed in one of the cages from birth to 6 months of age. Hang wire and adhesive removal tests were performed to evaluate somatosensory and motor performances. The extent of depression was determined by the forced swim test. Blood corticosterone levels were measured. In addition, brain malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) levels were analyzed. RESULTS: The depression-like behavior of the groups was similar. Although there were no significant differences in hang wire test among groups, CC500 group required longer durations in adhesive removal test. The body weight and plasma corticosterone levels of CC800 group were significantly higher than other groups. The oxidative stress parameters were highest in CC500 cage. CONCLUSIONS: Our study showed that the least stressful housing condition was IVC cage systems. Interestingly, the number of mice in the classical cages had a significant effect on stress levels and sensory-motor performance.
RESUMO
OBJECTIVE: Myositis, an inflammatory disease affecting muscles, is a rare and potentially fatal immune-related adverse event associated with immune checkpoint inhibitors. There are limited data on its clinical features and management. CASE PRESENTATION: Atezolizumab, in combination with etoposide and carboplatin, was initiated in the patient diagnosed with metastatic small-cell lung cancer. After four cycles, maintenance atezolizumab was initiated. At the third visit of the maintenance therapy, the patient reported weakness, edema, and tightness in the muscles that had progressed over the course of a week. Mild solid-food dysphagia was also observed. Neutrophilic leukocytosis with elevated creatine phosphokinase (9234â U/L), erythrocyte sedimentation rate (111â mm/h), and transaminase levels were observed. A diagnosis of myositis was considered based on clinical findings. Atezolizumab was omitted and an oral 0.5â mg/kg/day dose of methylprednisolone was administered. The myositis resolved within 10 days. During the treatment of myositis, the patient underwent prophylactic cranial irradiation. The steroid dose was tapered off within 35 days and then atezolizumab was restarted. CONCLUSION: The literature contains only a few case reports about atezolizumab-induced myositis, highlighting the challenges in defining its clinical features and management. Prompt diagnosis and treatment are crucial to prevent severe complications, such as myocarditis or respiratory muscle paralysis.
Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Miosite , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Antineoplásicos Imunológicos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Miosite/induzido quimicamente , Miosite/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
Objective: Total aortic arch replacement (TAR) necessitates hypothermic circulatory arrest (CA). The frozen elephant trunk technique (FET) additionally requires commercial hybrid grafts. Herein we describe a novel modified FET technique without CA using standard grafts thanks to left axillary artery (LAxA) cannulation in patients with acute type A aortic dissection. Methods: LAxA anastomosis is made first using a homemade debranching graft, and cardiopulmonary bypass is initiated, followed by anastomoses of left common carotid and innominate arteries. The rest of the operation is performed with complete cerebral perfusion. Following replacement of ascending aorta/root, cardiac reperfusion is started using a root cannula which continues throughout the procedure. Distal arch anastomosis is performed clamp-on, allowing lower body perfusion via left subclavian artery. Lower body perfusion is interrupted for 5 to 8 minutes to deploy an endograft to complete a modified FET. Following cannulation of distal arch graft, perfusion of distal aorta is restarted, and all three grafts are incorporated to construct a neo-ascending aorta and arch. Results: Between December 2018 and May 2022, 38 patients underwent TAR without operative mortality. Hospital mortality was %15.7, and spinal cord ischemia and stroke were not encountered in surviving patients. The mean lower body CA time was 7.2 ± 2.8 minutes. Conclusions: TAR using standard endografts without CA is possible with LAxA cannulation. To perform a FET, only a short interruption of lower body circulation is sufficient to deploy an endograft, also improving hemostasis of distal anastomosis. Further studies are required with a higher number of patients to evaluate the efficiency of this novel technique.
RESUMO
No studies have evaluated the interaction, quality, and reliability of chemotherapy-related videos published on YouTube. The aim was to evaluate the content of YouTube videos about chemotherapy using 5 different scoring tools. In this cross-sectional register-based study, popular videos on YouTube about the following keywords were examined; "chemotherapy," "what is chemotherapy," "types of chemotherapy," "chemotherapy side effects" and "chemotherapy treatments." Quality and reliability of video content were measured using the modified DISCERN (mDISCERN), the Journal of the American Medical Association (JAMA), the Global Quality Score (GQS), the Video Information Quality Index (VIQI), and Health on the Net code (HONcode) scores. A total of 108 videos were analyzed in the study. The median duration was 200 (30-2020) seconds and the median total number of views was 17500 (61-8615000). Among the video publishers, private hospitals were the most (n = 36, 33%). The most (n = 71, 66%) populer category of videos were patient education videos. Half (n = 55, 51%) of the narrators in the videos were only oncology professionals. Mean DISCERN, JAMA, GQS, VIQI, and HONcode scores were 2.73 ± 1.18, 1.97 ± 1.05, 2.94 ± 1.08, 14.03 ± 3.73, and 4.68 ± 2.46, respectively. A positive correlation was found between the 5 scoring points (P < .001 for all pairwise comparisons). There was a significant difference between video quality scores according to video categories and video publishers (P < .001 for both). Although most YouTube videos about chemotherapy were helpful to patients, content quality and reliability were moderate-low. Cancer patients looking for information on chemotherapy may find YouTube videos beneficial, but clinicians must be cautious to clear up any misunderstandings.